A diagnostic dilemma of intracranial pathology: coincidence or the result of cranial trauma?

A 21-year-old man presented to the accident and emergency department at St Peter's Hospital, London, in September 2008. Following consumption of alcohol, the patient had been assaulted and had experienced facial trauma. Later, the patient had a witnessed generalised tonic-clonic seizure and the next day noted weakness of the right leg. A CT scan of the brain revealed a solitary lesion in the left presylvian region close to the vertex, involving the leg area of the primary motor cortex. A subsequent MRI scan showed the lesion to be a cavernous haemangioma. The patient had no history of epilepsy. This raised the question as to whether the assault caused the lesion to haemorrhage, resulting in the seizure and spastic monoparesis, or did the formerly asymptomatic cavernoma bleed spontaneously with the assault being coincidental?

Multiple mitochondrial DNA deletions in monozygotic twins with OPMD.

BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is caused by expansions of the poly (A) binding protein 2 (PABP2) gene. Previous histological analyses have revealed mitochondrial abnormalities in the muscles of OPMD patients but their significance remains uncertain. OBJECTIVE: We had the rare opportunity to study monozygotic twins with identical expansions of the PABP2 gene but with markedly different severities of OPMD. Both had histological features of mitochondrial myopathy. We determined whether mitochondrial DNA abnormalities underlay these changes. METHODS: Clinical information was obtained by history and examination. Muscle biopsies were obtained from each subject and genetic analysis was performed using long-range PCR and Southern blotting. RESULTS: We demonstrate, for the first time, the presence of mitochondrial DNA (mtDNA) deletions by Southern blotting in individuals with OPMD. This correlates with the presence of mitochondrial myopathy in both twins. Moreover, both twins had different mtDNA deletions, which might explain their phenotypic differences. CONCLUSION: We hypothesise that mitochondrial dysfunction may occur as a consequence of PABP2 gene mutations, and that this dysfunction may affect the phenotypic manifestations of OPMD.

Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease.

BACKGROUND: Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis (or motor neuron disease). A range of antioxidant medications are available, and have been studied. OBJECTIVES: To examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials register (August 2005), MEDLINE (from January 1966 to August 2005), EMBASE (from January 1980 to August 2005) and other sources. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials of antioxidant treatment for amyotrophic lateral sclerosis. DATA COLLECTION AND ANALYSIS: The authors independently applied the selection criteria, assessed study quality and two authors performed independent data extraction. MAIN RESULTS: The search identified 23 studies for consideration but only nine studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure as the primary outcome measure, (survival at 12 months treatment). However, sufficient data were available from four studies to allow analysis of this outcome measure, and a meta-analysis was performed. In the individual studies no significant effect was observed for vitamin E 500 mg twice daily; vitamin E 1 g five times daily; acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 3 x 10-5g three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta-analysis of all antioxidants combined. No significant differences were demonstrated in any of the secondary outcome measures. AUTHORS' CONCLUSIONS: There is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in the treatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supported by the analysis we used. Generally the studies were poorly designed, and underpowered, with low numbers of participants and of short duration. Further well-designed trials of medications such as vitamin C and E are unlikely to be performed. If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial. The high tolerance and safety, and relatively low cost of vitamins C and E, and other considerations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use of these vitamins by physicians and people with amyotrophic lateral sclerosis. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.

Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease.

BACKGROUND: Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis (or motor neuron disease). A range of antioxidant medications are available, and have been studied. OBJECTIVES: To examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (July 2003), MEDLINE (from January 1966 to July 2003), EMBASE (from January 1980 to July 2003) and other sources. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials of antioxidant treatment for amyotrophic lateral sclerosis. DATA COLLECTION AND ANALYSIS: The reviewers independently applied the selection criteria, assessed study quality and two reviewers performed independent data extraction. MAIN RESULTS: The search identified 21 studies for consideration but only eight studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure, (survival at 12 months treatment). Sufficient data were available from three studies to allow analysis of the primary outcome measure, and a meta-analysis was performed. In the individual studies no significant effect was observed of vitamin E 500 mg twice daily; acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 3 x 10-5g three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta-analysis of antioxidants in general when combining the results. No significant differences were demonstrated in secondary outcome measures. AUTHORS' CONCLUSIONS: There is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in the treatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supported by the analysis we used. Generally the studies were poorly designed, and underpowered, with low numbers of participants and of short duration. Further well-designed trials of medications such as vitamin C and E are unlikely to be performed. If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial. The high tolerance and safety, and relatively low cost of vitamins C and E, and other considerations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use of these vitamins by physicians and patients. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.

Phenotypic variability in siblings with type III spinal muscular atrophy.

Autosomal recessive spinal muscular atrophy (SMA) shows substantial phenotypic variability, presenting at a variety of ages from infancy to adult life. Diagnostic difficulties may arise because SMA sometimes produces a dystrophic or myopathic phenotype rather than classical neurogenic abnormalities. Two brothers are described who illustrate this principle and highlight the increasing importance of molecular genetics in investigating patients with neuromuscular diseases. The findings are discussed in the light of recent observations in a mouse model of SMA.

Enterovirus related metabolic myopathy: a postviral fatigue syndrome.

OBJECTIVE: To detect and characterise enterovirus RNA in skeletal muscle from patients with chronic fatigue syndrome (CFS) and to compare efficiency of muscle energy metabolism in enterovirus positive and negative CFS patients. METHODS: Quadriceps muscle biopsy samples from 48 patients with CFS were processed to detect enterovirus RNA by two stage, reverse transcription, nested polymerase chain reaction (RT-NPCR), using enterovirus group specific primer sets. Direct nucleotide sequencing of PCR products was used to characterise the enterovirus. Controls were 29 subjects with normal muscles. On the day of biopsy, each CFS patient undertook a subanaerobic threshold exercise test (SATET). Venous plasma lactate was measured immediately before and after exercise, and 30 minutes after testing. An abnormal lactate response to exercise (SATET+) was defined as an exercise test in which plasma lactate exceeded the upper 99% confidence limits for normal sedentary controls at two or more time points. RESULTS: Muscle biopsy samples from 20.8% of the CFS patients were positive for enterovirus sequences by RT-NPCR, while all the 29 control samples were negative; 58.3% of the CFS patients had a SATET+ response. Nine of the 10 enterovirus positive cases were among the 28 SATET+ patients (32.1%), compared with only one (5%) of the 20 SATET- patients. PCR products were most closely related to coxsackie B virus. CONCLUSIONS: There is an association between abnormal lactate response to exercise, reflecting impaired muscle energy metabolism, and the presence of enterovirus sequences in muscle in a proportion of CFS patients.